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A Targeted Mass Spectrometric Analysis Reveals the Presence of a Reduced but Dynamic Sphingolipid Metabolic Pathway in an Ancient Protozoan, Giardia lamblia

Giardia lamblia, a single-celled eukaryote, colonizes and thrives in the small intestine of humans. Because of its compact and reduced genome, Giardia has adapted a “minimalistic” life style, as it becomes dependent on available resources of the small intestine. Because Giardia expresses fewer sphin...

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Autores principales: Duarte, Trevor T., Ellis, Cameron C., Grajeda, Brian I., De Chatterjee, Atasi, Almeida, Igor C., Das, Siddhartha
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6668603/
https://www.ncbi.nlm.nih.gov/pubmed/31396488
http://dx.doi.org/10.3389/fcimb.2019.00245
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author Duarte, Trevor T.
Ellis, Cameron C.
Grajeda, Brian I.
De Chatterjee, Atasi
Almeida, Igor C.
Das, Siddhartha
author_facet Duarte, Trevor T.
Ellis, Cameron C.
Grajeda, Brian I.
De Chatterjee, Atasi
Almeida, Igor C.
Das, Siddhartha
author_sort Duarte, Trevor T.
collection PubMed
description Giardia lamblia, a single-celled eukaryote, colonizes and thrives in the small intestine of humans. Because of its compact and reduced genome, Giardia has adapted a “minimalistic” life style, as it becomes dependent on available resources of the small intestine. Because Giardia expresses fewer sphingolipid (SL) genes—and glycosphingolipids are critical for encystation—we investigated the SL metabolic cycle in this parasite. A tandem mass spectrometry (MS/MS) analysis reveals that major SLs in Giardia include sphingomyelins, sphingoid bases, ceramides, and glycosylceramides. Many of these lipids are obtained by Giardia from the growth medium, remodeled at their fatty acyl chains and end up in the spent medium. For instance, ceramide-1-phosphate, a proinflammatory molecule that is not present in the culture medium, is generated from sphingosine (abundant in the culture medium) possibly by remodeling reactions. It is then subsequently released into the spent medium. Thus, the secretion of ceramide-1-phospate and other SL derivatives by Giardia could be associated with inflammatory bowel disease observed in acute giardiasis. Additionally, we found that the levels of SLs increase in encysting Giardia and are differentially regulated throughout the encystation cycle. We propose that SL metabolism is important for this parasite and, could serve as potential targets for developing novel anti-giardial agents.
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spelling pubmed-66686032019-08-08 A Targeted Mass Spectrometric Analysis Reveals the Presence of a Reduced but Dynamic Sphingolipid Metabolic Pathway in an Ancient Protozoan, Giardia lamblia Duarte, Trevor T. Ellis, Cameron C. Grajeda, Brian I. De Chatterjee, Atasi Almeida, Igor C. Das, Siddhartha Front Cell Infect Microbiol Cellular and Infection Microbiology Giardia lamblia, a single-celled eukaryote, colonizes and thrives in the small intestine of humans. Because of its compact and reduced genome, Giardia has adapted a “minimalistic” life style, as it becomes dependent on available resources of the small intestine. Because Giardia expresses fewer sphingolipid (SL) genes—and glycosphingolipids are critical for encystation—we investigated the SL metabolic cycle in this parasite. A tandem mass spectrometry (MS/MS) analysis reveals that major SLs in Giardia include sphingomyelins, sphingoid bases, ceramides, and glycosylceramides. Many of these lipids are obtained by Giardia from the growth medium, remodeled at their fatty acyl chains and end up in the spent medium. For instance, ceramide-1-phosphate, a proinflammatory molecule that is not present in the culture medium, is generated from sphingosine (abundant in the culture medium) possibly by remodeling reactions. It is then subsequently released into the spent medium. Thus, the secretion of ceramide-1-phospate and other SL derivatives by Giardia could be associated with inflammatory bowel disease observed in acute giardiasis. Additionally, we found that the levels of SLs increase in encysting Giardia and are differentially regulated throughout the encystation cycle. We propose that SL metabolism is important for this parasite and, could serve as potential targets for developing novel anti-giardial agents. Frontiers Media S.A. 2019-07-24 /pmc/articles/PMC6668603/ /pubmed/31396488 http://dx.doi.org/10.3389/fcimb.2019.00245 Text en Copyright © 2019 Duarte, Ellis, Grajeda, De Chatterjee, Almeida and Das. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
Duarte, Trevor T.
Ellis, Cameron C.
Grajeda, Brian I.
De Chatterjee, Atasi
Almeida, Igor C.
Das, Siddhartha
A Targeted Mass Spectrometric Analysis Reveals the Presence of a Reduced but Dynamic Sphingolipid Metabolic Pathway in an Ancient Protozoan, Giardia lamblia
title A Targeted Mass Spectrometric Analysis Reveals the Presence of a Reduced but Dynamic Sphingolipid Metabolic Pathway in an Ancient Protozoan, Giardia lamblia
title_full A Targeted Mass Spectrometric Analysis Reveals the Presence of a Reduced but Dynamic Sphingolipid Metabolic Pathway in an Ancient Protozoan, Giardia lamblia
title_fullStr A Targeted Mass Spectrometric Analysis Reveals the Presence of a Reduced but Dynamic Sphingolipid Metabolic Pathway in an Ancient Protozoan, Giardia lamblia
title_full_unstemmed A Targeted Mass Spectrometric Analysis Reveals the Presence of a Reduced but Dynamic Sphingolipid Metabolic Pathway in an Ancient Protozoan, Giardia lamblia
title_short A Targeted Mass Spectrometric Analysis Reveals the Presence of a Reduced but Dynamic Sphingolipid Metabolic Pathway in an Ancient Protozoan, Giardia lamblia
title_sort targeted mass spectrometric analysis reveals the presence of a reduced but dynamic sphingolipid metabolic pathway in an ancient protozoan, giardia lamblia
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6668603/
https://www.ncbi.nlm.nih.gov/pubmed/31396488
http://dx.doi.org/10.3389/fcimb.2019.00245
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